ArticleDiabetologia2016
The non-canonical NF-κB pathway is induced by cytokines in pancreatic beta cells and contributes to cell death and proinflammatory responses in vitro.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Glycosylation modification: a trigger for obesity and its complications?Molecular medicine (Cambridge, Mass.) · 2026Review
- Methylprednisolone Protects Human Pancreatic Beta Cells From Inflammation-induced Damage.Transplantation direct · 2025Article
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies.Chinese medical journal · 2025Review
- Associations between systemic inflammatory indices and the risk of renal function decline in patients with type 2 diabetes mellitus: a retrospective cohort study.Frontiers in endocrinology · 2025Article
- α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB Pathway.Inflammation · 2024Article
- Adipocyte-specific FAK deletion promotes pancreatic β-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.Clinical and translational medicine · 2024Article
- Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the path to osteoarthritis management: targeting chondrocyte apoptosis for therapeutic intervention.Frontiers in cell and developmental biology · 2024Review
- Mitochondrial dysfunction in pancreatic acinar cells: mechanisms and therapeutic strategies in acute pancreatitis.Frontiers in immunology · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- LncRNA ARGI Contributes to Virus-Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN-Stimulated Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Insulin/IGF Axis and the Receptor for Advanced Glycation End Products: Role in Meta-inflammation and Potential in Cancer Therapy.Endocrine reviews · 2023Review
- Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in β-cell subpopulations associated with glycemic control.BMC genomics · 2023Article
- The selective serotonin reuptake inhibitor fluoxetine has direct effects on beta cells, promoting insulin secretion and increasing beta-cell mass.Diabetes, obesity & metabolism · 2022Article
- NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes.Cell death & disease · 2022Article
- ROCK inhibitor fasudil reduces the expression of inflammatory factors in LPS-induced rat pulmonary microvascular endothelial cells via ROS/NF-κB pathway.BMC pharmacology & toxicology · 2022Article
- A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
aims/hypothesisActivation of the transcription factor nuclear factor (NF)-κB by proinflammatory cytokines plays an important role in beta cell demise in type 1 diabetes. Two main signalling pathways are known to activate NF-κB, namely the canonical and the non-canonical pathways. Up to now, studies on the role of NF-κB activation in beta cells have focused on the canonical pathway. The aim of this study was to investigate whether cytokines activate the non-canonical pathway in beta cells, how this pathway is regulated and the consequences of its activation on beta cell fate.
methodsNF-κB signalling was analysed by immunoblotting, promoter reporter assays and real-time RT-PCR, after knockdown or overexpression of key genes/proteins. INS-1E cells, FACS-purified rat beta cells and the human beta cell line EndoC-βH1 exposed to cytokines were used as models.
resultsIL-1β plus IFN-γ induced stabilisation of NF-κB-inducing kinase and increased the expression and cleavage of p100 protein, culminating in the nuclear translocation of p52, the hallmark of the non-canonical signalling. This activation relied on different crosstalks between the canonical and non-canonical pathways, some of which were beta cell specific. Importantly, cytokine-mediated activation of the non-canonical pathway controlled the expression of 'late' NF-κB-dependent genes, regulating both pro-apoptotic and inflammatory responses, which are implicated in beta cell loss in early type 1 diabetes. CONCLUSIONS/
interpretationThe atypical activation of the non-canonical NF-κB pathway by proinflammatory cytokines constitutes a novel 'feed-forward' mechanism that contributes to the particularly pro-apoptotic effect of NF-κB in beta cells.
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